Project 1 is responsible for clinical studies of physiological phenotypes related to schizophrenia. The aim of Centers for Neuroscience of Mental Disorders is to bring basic science expertise to bear upon chronic mental disorder. However, these disorders are complex, multi-faceted syndromes that are not immediately amenable to basic science investigation. This project is responsible for identifying discrete deficits in schizophrenics that may more directly represent neuronal dysfunction, so that other projects can use these deficits for genetic and molecular studies, for study in isolated tissue, and for modeling in animals. Project 1 is also responsible for testing in human subjects any hypotheses reached from basic science research. Two physiological measures will be used for most studies: deficits in smooth pursuit eye movements and diminished inhibitory gating of the P50 auditory evoked potential response. Three experiments will be performed: (1) linkage studies using these measures in collaboration with Project 2, along with clinical diagnoses, to determine if one or more of these phenotypes identifies genes relevant to the transmission of schizophrenia; (2) studies of the effects of nicotine on the measures, to determine if nicotine normalizes the defects, as predicted by Project 3's animal model; and (3) investigations to define factors, such as increased catecholamine metabolism, that cause variability in these measures, to improve their usefulness for clinical research. In addition, Project 1 collects post mortem and aborted tissue specimens for Projects 6 and 7.